Low-intensity muscle contraction exercise following the onset of arthritis improves hyperalgesia via reduction of joint inflammation and central sensitization in the spinal cord in a rat model

Ishikawa, Kumiko; Kajiwara, Yasuhiro; Sakamoto, Juichi; Sasaki, Ryo; Goto, Kyo; Honda, Yukiharu; Kataoka, Hideki; Okita, Minoru

doi:10.1016/j.neulet.2019.04.031

Cited by 16 publications

(15 citation statements)

References 26 publications

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“…Micrographs were obtained at 200x magnification, and the spinal dorsal horn was divided into the superficial (lamina I-II) and deeper (lamina III-VI) layers, according to previously described criteria [ 14 ]. Our previous study indicated how to quantitative analysis for immunostaining of CGRP in the spinal dorsal horn [ 15 ]. Briefly, the border between the superficial and the deeper layers was defined by the occurrence of transverse fibers in lamina III.…”

Section: Methodsmentioning

confidence: 99%

Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw

Ishikawa

Oga

Goto

et al. 2021

Pain Research and Management

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Voluntary exercise is sufficient to protect against neuropathic pain. However, it is unclear whether voluntary exercise reduces immobilization-induced hyperalgesia. We examined the effect of voluntary forelimb exercise on immobilized-induced hyperalgesia in hind paws of rats. Wistar rats were randomly divided into the (1) both hind limbs immobilized group (IM group), (2) immobilization and exercise with nonimmobilized fore limbs group (EX group), and (3) control group. In the IM and EX groups, the bilateral ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for eight weeks. In the EX group, voluntary exercise using nonimmobilized forelimbs in the running wheel was administered during the immobilization period, while hind limbs were kept immobilized (60 min/day, 5 days/week). Mechanical hyperalgesia in the hind paw was measured using a digital von Frey device every week. To investigate the abnormality of primary sensory neurons and central sensitization, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide in the spinal dorsal horn were analyzed by immunohistochemical staining. Immobilization-induced mechanical hyperalgesia was inhibited in the EX group compared to the IM group at three weeks after immobilization. In the EX group, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide were significantly decreased compared to those in the IM group. Our results therefore suggest that voluntary forelimb exercise during hind limb immobilization partially reduces immobilization-induced hyperalgesia by suppressing that the plastic changes of the primary sensory nerves that excessively transmit pain and increased responsiveness of nociceptive neurons in the spinal dorsal horn.

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Section: Methodsmentioning

confidence: 99%

Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw

Ishikawa

Oga

Goto

et al. 2021

Pain Research and Management

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“…As the pressure increased, values were recorded when rat lifted and pulled back of the paw or vocalized. 21 Each rat was tested three times with an interval of 10 min. The average PPT was calculated.…”

Section: Methodsmentioning

confidence: 99%

Pressing Intervention Promotes the Skeletal Muscle Repair of Traumatic Myofascial Trigger Points in Rats

Jiang¹,

Xiang²,

Liú³

et al. 2021

JPR

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Objective: To observe the effect of pressing intervention on the skeletal muscle repair of myofascial trigger points (MTrPs) in rats and explore the mechanism of pressing intervention on the deactivation of trigger points. Methods: Thirty SPF rats were randomly divided into blank group, model group and press group, with 10 rats in each group. The MTrPs models were established by blunt striking plus eccentric exercise, and then evaluated. The press group was given a pressing intervention with a self-made device for 14 days, and the rats in the other two groups were fed normally. Soft tissue tension (STT) D 0.2 and pressure pain threshold (PPT) were measured before and after intervention. The skeletal muscle tissue at MTrPs was extracted and assessed by hematoxylin-eosin (HE) and Masson staining. The expression of collagen I, collagen III, α-smooth muscle actin (α-SMA), myosin heavy chain (MHC) and fibronectin (FN) were detected by Western Blotting. Enzyme linked immunosorbent assay (ELISA) was used to evaluate the expression of substance P (SP), 5-hydroxytryptamine (5-HT), cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2). Results: (1) Compared with the blank group, the PPT and D 0.2 reduced (P < 0.05) in the model group; while compared with the model group, the PPT and D 0.2 increased (P < 0.05) in the press group. (2) Compared with the blank group, the model group showed obvious spontaneous potentials with higher amplitude and frequency, which were also much higher than those of the press group (P < 0.05). (3) The HE and Masson staining results showed evident fibrosis in the muscle tissue of the model group, with a larger area of collagen fibers relative to that of the press group (P < 0.05). ( 4) The amount of collagen I, collagen III, FN, α-SMA, SP, 5-HT, COX-2 and PGE2 increased and the content of MHC decreased (P < 0.05) in the model group, as compared to the blank group; while all the substances (P < 0.05), instead of MHC which increased (P < 0.05), in the press group were decreased as compared to the model group. Conclusion:Pressing intervention on the MTrPs in rats can alleviate chronic inflammation, inhibit fibrosis, promote skeletal muscle repair and relieve pain.

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“…was applied in the inflamed hind paw with a digital recording of the increasing pressure. 19 The corresponding pressure (in g) was recorded whenever there was a hind paw flection reflex or vocalization. Three measurements were carried out on the same location at intervals of more than ten minutes, and the average was calculated as the PPT and adopted for statistical analysis.…”

Section: Pressure Pain Threshold (Ppt) Measurementmentioning

confidence: 99%

“…Decalcified with 0.5 M EDTA and dehydrated with graded ethanol, each specimen was paraffin embedded. 19 Coronally sectioned at 4μm thickness, slices were stained with H&E, photographed using a cool CCD camera connected to a Zeiss Axioskop 2 plus microscope (Carl Zeiss Microimaging) and evaluated by two blinded investigators. The L4-L6 dorsal root ganglias (DRGs) and synovial tissue in left joints of all the rats were excised and instantly frozen at −80°C for subsequent experiments.…”

Section: Sample Preparationmentioning

confidence: 99%

<p>Dexamethasone-Loaded Thermosensitive Hydrogel Suppresses Inflammation and Pain in Collagen-Induced Arthritis Rats</p>

Wang¹,

Xu²,

Fan³

et al. 2020

DDDT

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To overcome negative adverse effects and improve therapeutic index of dexamethasone (Dex) in rheumatoid arthritis (RA), we developed a novel sustained release formulation-intra-articular injectable dexamethasone-loaded thermosensitive hydrogel (DLTH) with chitosan-glycerin-borax as carrier for the remission of inflammation and pain. The focus of this article is to explore both anti-inflammatory and pain-relieving effects of DLTH joint injection in bovine type-II collagen-induced arthritis (CIA) rats. Methods: Wistar rats were randomized into three groups, including the normal group (n=6), the model group (n=6) and the DLTH group (n=10). Joint injection of DLTH (1mg/kg Dex per rat) was injected on day 12 in the DLTH group twice a week for three weeks. Clinical signs of body weight, paw swelling and arthritis scores, histologic analysis, hind paw mechanical withdrawal threshold (MWT), plantar pressure pain threshold (PPT) were taken into consideration. Serum contents of IL-17A, prostaglandin E2 (PGE2), prostacyclin 2 (PGI2) and prostaglandin D2 (PGD2), real-time polymerase chain reaction (PCR) analysis of inflammatory factors and pain-related mediators in synovium and dorsal root ganglia (DRG), Western blotting of NF-κB in synovium were all evaluated. Results: Paw swelling, arthritis scores and joint inflammation destruction were all attenuated in the DLTH-treated group. Results showed that DLTH not only down-regulated serum IL-17A, but also mRNA levels of inflammatory factors and NGF, and key proteins contents of the NF-κB pathway in synovium. Increases of MWT and PPT in DLTH-treated rats elucidated pain-reducing effects of DLTH. Elevated serum PGD2 levels and declines of serum PGE2 and PGI2, and inflammatory and pain-related genes in DRGs in the DLTH group were also recorded. Conclusion: These data elucidated that DLTH joint injection impeded synovial inflammation processes through down-regulating transcription activity of NF-κB pathway, and intraarticular DLTH may aid in the regulation of RA pain through regulating inflammation and pain conduction process.

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Low-intensity muscle contraction exercise following the onset of arthritis improves hyperalgesia via reduction of joint inflammation and central sensitization in the spinal cord in a rat model

Cited by 16 publications

References 26 publications

Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw

Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw

Pressing Intervention Promotes the Skeletal Muscle Repair of Traumatic Myofascial Trigger Points in Rats

<p>Dexamethasone-Loaded Thermosensitive Hydrogel Suppresses Inflammation and Pain in Collagen-Induced Arthritis Rats</p>

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